A genome of kinds of bacteria and yeast (i.e. base sequence of the entire genes) has been determined in late years, and a human genome would be determined completely in the near future. Such a rapid progress of the genome sequencing technology makes it possible to clarify functions of the determined genes and functions of proteins derived from the determined genes. It is said that the number of genes of yeast is approximately 6,200 and the number of genes of human being is approximately 100,000. Thus, a technology for manipulating at the same time a vast number of genes such as proteins and others is needed for making clear these functions. The microarray technology has been rapidly developed in these years for accomplishing the above object and has attracted great attentions. The object of this technology is to achieve experimental systems for synthesizing a number of oligonucleotides on substrates such as slide glasses and for immobilizing cDNAs or proteins. For example, there has been developed an experimental system, in which a large number spot of cDNAs of all genes (genome) are disposed on one piece of slide glass, these spots are hybridized, and an intensity of the hybridization of respective spots is measured to determine expressions of respective genes.
For instance, U.S. Pat. No. 5,445,934 discloses a DNA chip including synthesized oligonucleotide on a substrate at a rate of not less than 1,000 spots/cm2. Furthermore, “Nature Genetic Supplements”, Vol. 21 (Patrick O. Brown et al. p33–37; David D. L. Bowtell p25–32, 1999, January) discloses a method for spotting cDNA solutions on a slide glass using a pin. Also, U.S. Pat. No. 5,807,522 discloses a method for spotting cDNA solutions on a slide glass using a solenoid vibrating the solutions.
There have been proposed the following methods of manufacturing microarrays:    (1) Photo-lithography method    (2) Micro spotting method    (3) Ink-jet method.
In the method (1), oligonucleotides are synthesized on a substrate using the same photo-lithography technology as that employed for manufacturing a semiconductor device. In the method (2), solutions of cDNAs and the like are spotted on a substrate using a pin-like tool. In the method (3), solutions of cDNAs, etc. are dropped from a narrow nozzle using a piezoelectric transducer and so on.
According to the method (1), successive spots can be placed at an interval of about 50–25 μm to manufacture a microarray having a high spot density. However, in this method, since an oligonucleotide is synthesized on the substrate, this method could not be applied to cDNAs which have been prepared separately. In addition, it takes a long time to design and manufacture a photomask, and thus this method is very expensive. In the methods (2) and (3), while these methods can be applied to cDNAs which have been prepared separately, a diameter of resulting spots is relatively large such as approximately 300–150 μm, and therefore, it is hard to manufacture a microarray with a high spot density. Owing to the reason that these methods require mechanically operation, they are suitable for manufacturing chips in small quantity, but are not suited for manufacturing chips in mass production. According to a document (Vivian G. Cheung et al. “Nature Genetic Supplements” 1999, January), if a size of a spot is reduced from 200 μm to 50 μm, a quantity of sample needed for making a chip goes down to about 1/100. Thus, upon realizing a practical microarray, one of critical problems to be solved is that how to reduce a spot size in order to obtain a chip with a high spot density.
In order to make clear functions of various genes or proteins and to use these findings in researching new drugs, diagnosing diseases and selecting optimal drugs for individual persons and so on, a microarray containing cDNAs or proteins must be manufactured with a small spot size and a high spot density at low cost. Therefore, the present invention is to provide a device for manufacturing a high spot density microarray having a spot size (i.e. diameter) of several μm to several tens μm by using one or more samples which have been prepared separately.
In PCT international publication WO98/58,745 and a document “Analytical Chemistry”, Vol. 71′ (Morozov et al. pp. 1415–1420, pp. 3110–3117, 1999)′, there have been proposed a device and a method for making solid spots or a film on a substrate by using the electrostatic spray, while the biologically activities of biomolecules such as a nucleic acid or a protein has are retained. A method and a device for manufacturing a microarray with very small spots simultaneously by adjusting various conditions have been also disclosed. However, since these method and device use a filter in the form of mesh, they could not provide a microarray, in which various samples are located at desired positions.